Light intermediate chain 1 defines a functional subfraction of cytoplasmicdynein which binds to pericentrin

The light intermediate chains (LICs) of cytoplasmic dynein consist of multi ple isoforms, which undergo post-translational modification to produce a la rge number of species separable by two-dimensional electrophoresis and whic h we have proposed to represent at least two gene products. Recently, we de monstrated the first known function for the LICs: binding to the centrosoma l protein, pericentrin, which represents a novel, non-dynactin-based cargo- binding mechanism. Here we report the cloning of rat LIC1, which is approxi mately 75% homologous to rat LICE and also contains a P-loop consensus sequ ence, We compared LIC1 and LICE for the ability to interact with pericentri n, and found that only LIC1 will bind. A functional P-loop sequence is not required for this interaction. We have mapped the interaction to the centra l region of both LIC1 and pericentrin. Using recombinant LICs, we found tha t they form homooligomers, but not heterooligomers, and exhibit mutually ex clusive binding to the heavy chain. Additionally, overexpressed pericentrin is seen to interact with endogenous LIC1 exclusively. Together these resul ts demonstrate the existence of two subclasses of cytoplasmic dynein: LIC1- containing dynein, and LIC2-containing dynein, only the former of which is involved in pericentrin association with dynein.